DESCRIPTION: (provided by the applicant): The potential for an arboviral infection to develop and progress to symptomatic, and perhaps fatal disease, may be greatly enhanced when a virus is transmitted naturally by an arthropod vector. Viruses and vector salivary gland substances may be delivered cutaneously. Langerhans cells and dendritic cells are thus likely to be involved in host recognition of virus and salivary substances, and in antigen presentation to macrophages and T and B cells. The primary function of salivary products is to facilitate blood feeding, but they also modulate immune molecules. Salivary substances therefore impact upon the same factors that determine the outcome of arboviral infection. Using Dengue 2 and West Nile viruses with their respective vectors (Aedes aegypti and Culex pipiens) the PI will address three specific aims: 1) To examine the effect of mosquito feeding and salivary products on viral infection in flavivirus-susceptible C3H/HeJ mice and flavivirus-resistant C3H/RV mice; 2) To determine the effect of mosquito feeding and salivary proteins on key components of the host immune system at the site of feeding/infection and at their draining lymph nodes; 3) To define mechanisms involved in salivary modulation of arboviral infection via the administration of neutralizing anti-saliva antibodies prior to infection, and by manipulated mosquitoes to alter the expression levels of specific salivary product(s). Proposed experiments will lead to a better understanding of the virus-vector-host interactions and will identify avenues of intervention to control transmission and pathology resulting from arbovirus infections. This knowledge may contribute towards the development of a mouse model for human dengue infections.